New HIV-1 circulating recombinant forms are increasingly reported. This finding is significant because it suggests that HIV co-infection occurs in vivo. The mere fact is crucial for a future treatment approach to HIV-positive patients, for researches towards a definite cure and the public health strategy.
A 38-year-old male with an acute retroviral syndrome (ARS) following previous multiple unprotected sexual contacts with male partners was presented at the clinic. The person was included into the Quest trial (AZT, 3TC, Abacavir, Amprenavir for 25 months, with from 19 to 25 months, vaccination by Alvac vCP 1452 and stop all treatment at month 25). During the therapy, viremia declined from >106 HIV-1 RNA copies/ml (c/mL) and remained <200 c/mL while the patient was on HAART. A month after ending the treatment, viremia rebounded to 80’000 c/mL, then declined to 20’000 c/ml and raised again, two weeks later, at 200’000c/ml (second rebound), to finally fluctuate between 200’000-400’000 c/mL for five months before HAART re-initiation. Patient manifested worsening of the clinical picture, and the diagnostic procedure had begun.
Protease (Pr), reverse transcriptase (RT) gag and C2V3 gene sequencing documented an initial infection by subtype AE during the ARS.Subtype B rapidly replaced AE at the time of the second rebound. To discriminate between co-infection and super-infection we set up a subtype-specific PCR (end Pr-proximal third of RT) using subtype specific primers for AE and B designed according to patient’s sequences. The subtype-specific PCR confirmed:
One/ the absence of B subtype in both plasma and proviral DNA before the second viremia rebound
Two/ the emergence, during the second rebound and later on of B subtype as the majority subtype in both DNA and plasma. The C2V3 sequences of the B subtype were related to B Brazilian strains. This correlates with a Brazilian trip of the patient where several unprotected sexual contacts three weeks before B emergence took place. In in vitro cultures B subtype primary isolate had a much higher replicative capacity than AE subtype.
Declined viremia during HAART indicates the sensitivity of this HIV-positive patients to combined antiretroviral drugs, and this refers to previously diagnosed AE subtype of HIV. The subsequent increase of viremia following interruption of HAART correlates with the first phase of superinfection. B subtype of HIV is responsible for the second rebound and worsening of the clinical manifestations due to B subtype takeover in the bloodstream. This patient suffered two separate HIV infections caused by two different subtypes of virus in different periods of time, which strongly suggests that superinfection is possible in vivo and manifests amazing genetic diversity of HIV.
The case described above is considered to be the first documented case of HIV-1 superinfection. These findings have a great importance for a general approach to HIV treatment and for various researches striving to create a definite cure for this disease. In the case of increased percent of superinfections, genetic diversity of HIV-1 would become even more complex. That would aggravate the vaccine development and the searches for an effective cure. Finally, the possibility of super-infection would alternate public health strategies.